In dogs, the source and nature of the hepatotrophic substances in the splanchnic venous blood previously described from this laboratory will be looked for. Experiments will be performed whereby the venous drainage from different abdominal organs will be directed to one fraction of the liver at the same time as the venous return from other organs will supply the portal inflow to the rest of the liver. From experiments already performed, there is evidence that the hepatotrophic substances eminate from the pancreas, and our hypothesis is that they are hormonal and specifically, insulin and glucagon. To assess the role of these hormones in controlling hepatic structure, function and regeneration, enzyme analyses in liver fragments with variable blood supply will be obtained with the principal emphasis upon the cyclic AMP secondary messenger system. When the role of hormones as hepatotrophic factors is established, further experiments have been designed in which the influence of insulin will be removed without otherwise damaging the pancreas by the creation of alloxan or streptozocin diabetes. Alternatively, the effects of exogenous insulin (or glucagon) upon the liver tissue will be assessed under conditions of chronic infusion.